Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

avWD is a rare entity that is primarily associated with lymphoproliferative disorders, most commonly with multiple myeloma, lymphoma, and the myeloproliferative diseases. Various pathogenetic mechanisms have been postulated. The most commonly seen is antibodies directed against the FVIII complex, resulting in either its accelerated destruction or its accelerated clearance by the reticuloendothelial system. There may be immunoadsorption of the FVIII complexes onto the clones of malignant cells, as has been reported in several cases, or proteolysis may be causing the peripheral destruction of the FVIII complex. Lastly, as seen in hypothyroidism, global decrease in production of the multimers also results in avWD. The treatment, in general, should be aimed at controlling the underlying disorder and at stopping any life-threatening hemorrhage. The treatment includes any or all of the following: DDAVP, cryoprecipitate, FVIII concentrates, extracorporeal immunoadsorption, and chemotherapy as needed to control the underlying disorders. The screening tests that will allow for the detection of the avWD include measurement of the bleeding time, the FVIII:C, FVIII:vWF, and the FVIII:RCoF. FVIII:C inhibitors can be demonstrated by mixing the patient plasma with normal plasma. A normal prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) are expected. Clinically, these patients present with mucosal bleeding, and in avWD tend to have an association with lymphoproliferative malignancies. They tend to be elderly patients with no prior history of bleeding diathesis and to have negative family histories for coagulopathies. Further study of these patients is warranted, because this disorder appears to have a multifactorial etiology. Increasing our understanding of avWD may increase our understanding of congenital vWD, thus allowing us to more effectively treat all patients with von Willebrand's disease.
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PMID:Acquired von Willebrand's disease. 145 20

Ageing does not bring with it any major changes in the coagulation or fibrinolytic proteins or platelets. It does bring a greater burden of disease, with less reserves, and so when haemorrhage occurs in the elderly it has more serious consequences. The cause of a bleeding diathesis can usually be determined after a careful history, and examination of the patient followed by simple tests--the platelet count, blood film, bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and the euglobulin clot lysis time. Other confirmatory tests, assays and inhibitor titres, will seal the diagnosis. Treatment is mainly directed at removing the underlying cause, if possible, and remedying the defect, with platelet transfusion, fresh frozen plasma or factor concentrates. These treatments will not be effective where there is an inhibitor or antibody present; steroids, splenectomy (for ITP), plasma exchange or immunosuppression are needed. Two major advances have occurred in the early 1980s. One has been the introduction of high-dose intravenous immunoglobulin in the management of ITP, although worries remain about thrombotic events in elderly patients. The other is the spreading use of DDAVP, originally introduced for von Willebrand's disease and mild haemophilia, and now finding a role in uraemia and with cardiopulmonary bypass. Drugs are a significant and potentially preventable cause of bleeding in the elderly. The most frequent problems arise with anticoagulants. The risk of interactions increase with the number of other medications which are prescribed.
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PMID:Bleeding and coagulation disorders in the elderly. 332 49

The prolonged partial thromboplastin time observed in the plasma of a 36 year old asymptomatic man was related to the reduced prekallikrein activities (coagulant; antigenic; and amidolytic) and the absence of coagulant and immunologic activities of high molecular weight kininogen (HMWKg). The patient's plasma also exhibited impaired surface-mediated fibrinolysis and impaired generation of kallikrein. The coagulation defect was identified as the "Fitzgerald trait". The levels of CH50, C2, C4 and C-1 inactivator were normal. Venous occlusion in the patient gave rise to a normal release of extrinsic plasminogen activator from the vascular endothelium. The administration of DDAVP led to a FVIII/VWF response which was similar to that obtained in healthy subjects. No alteration could be observed in the contact phase proteins after DDAVP administration.
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PMID:New congenital deficiency of high molecular weight kininogen and prekallikrein (Fitzgerald trait). Study of response to DDAVP and venous occlusion. 363 67

Von Willebrand's disease (vWD) is the most common inherited bleeding disorder. Typical clinical features such as bleeding after surgery or trauma might suggest the disease. We present a series of 24 patients with vWD treated between 1989 and 1992. Diagnosis was confirmed by a reduction in plasma factor VIII antigen concentration, reduction of ristocetin cofactor activity and reduced factor VIII activity. Seventeen of the patients underwent surgery (7 adenoidectomies, 8 tonsillectomies, 2 paranasal sinus operations) and received preoperative stimulation of von Willebrand factor (vWF) using DDAVP. This resulted in a rapid increase in plasma vWF concentration from an average of 56% before stimulation to 190% of the normal value after stimulation. A reduction of partial thromboplastin time from an average of 44.4 seconds to 34.4 seconds was observed following DDAVP. No bleeding complications or other side-effects occurred. Preoperative stimulation of vWF using DDAVP proved to be a safe method to reduce the risk of bleeding in patients with vWD undergoing surgery.
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PMID:[Von Willebrand syndrome--risk of hemorrhage in ENT interventions in childhood]. 806 Apr 55

We report a family with a combined factor VII Padua defect and von Willebrand's disease (vWd). The propositus is a 9-year-old child with a moderate bleeding tendency who appeared to be heterozygous for both factor VII Padua and type I vWd. The diagnosis of factor VII Padua was based on a normal factor VII antigen and factor VII activity which was low with rabbit brain thromboplastin but normal with ox brain thromboplastin. Type I vWd was diagnosed because of a concomitant decrease of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin-cofactor activity (vWf:RCoF), associated with the presence of vWf multimers of all sizes in plasma and platelets. The parents were not consanguineous but came from the same isolated river Piave valley in North Eastern Italy where the factor VII Padua defect was first described. The father had the factor VII Padua defect but was clinically asymptomatic in accordance with the heterozygous state. The propositus's mother had type I vWd and was mildly symptomatic. The propositus' sisters, who were clinically asymptomatic, were both heterozygotes for factor VII Padua. The infusion of DDAVP normalized the factor VIII/vWf pattern in all patients. In the propositus, in contrast to the mother and normal subjects, showed a more rapid clearance both of vWf and factor VIII. The same pattern, albeit to a lesser degree, was also observed in the father.
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PMID:First report of combined factor VII Padua defect and von Willebrand's disease due to casual association of the two defects. 845 48

As in adults, desmopressin (DDAVP) can be used in children for prophylaxis of bleeding and to stop bleeding in many hereditary and acquired bleeding disorders. DDAVP is the treatment of choice in children with mild hemophilia and type 1 von Willebrand's disease (vWD). It is effective in some variants of vWD and in many patients with platelet function defects. It reduces the bleeding diathesis of children with uremia and drug-induced bleeding complications. In any case, a test dose of DDAVP has to be given to the patient to predict the hemostatic effect before relying on this drug for treatment. The response can be measured by shortening of the bleeding time (BT) and of partial thromboplastin time (PTT), indicating a rise of Factor (F) VIII or von Willebrand factor (vWF). Side effects such as facial flushing, transient headache, increased pulse rate, and drop in systolic blood pressure are mild and transient. They can be minimized when the dose is not exceeding 0.3 microg/kg body weight, and the infusion lasts at least 20 to 30 minutes. The strong antidiuretic action of DDAVP has some potential problems that are negligible in adults and older children when water intake is restricted. In infants and small children under the age of 18 months, however, DDAVP should be used with caution and with close surveillance in order to prevent water intoxication and electrolyte imbalance. The danger is increased when the patients receive parenteral fluid substitution. The advantages of DDAVP include the reduction in the use of plasma factor concentrates, thereby minimizing the danger of immunological or infectious complications, as well as the considerable reduction of costs realized by treatment with this form of medication. Fortunately, it can be applied successfully in the most frequent hereditary bleeding disorder, namely vWD type 1.
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PMID:Desmopressin (DDAVP) in bleeding disorders of childhood. 1006 51

We tested the response to desmopressin (1-deamino-cys-8-D-arginine-vasopressin; DDAVP) in four patients with haemophilia B [factor IX (F IX) at diagnosis 1.4-5%]. The activated partial thromboplastin time (aPTT) was significantly shortened in all patients. Although there was an up to 1.4-fold increase in F IX levels in three patients, maximal F IX activity remained below 10%. Much more prominent were the increases in F VIII (three- to fourfold), in von Willebrand factor antigen (VWF:Ag; 2.5-fold) and particularly in VWF collagen-binding activity (VWF:CBA; fivefold). These changes were reflected by the prophylactic efficacy of DDAVP for dental surgery. After pretesting, DDAVP could be a useful drug for reducing the need for plasma products for prevention of minor surgical bleeding in patients with mild to moderate haemophilia B.
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PMID:DDAVP (desmopressin; 1-deamino-cys-8-D-arginine-vasopressin) treatment in children with haemophilia B. 1155 8

Factor XI deficiency is a rare inherited coagulation disorder. It rarely produces spontaneous bleeding although patients with this disorder are at risk for hemorrhagic complications after trauma or surgery. Because there is no clear correlation between the tendency to bleed and the severity of the disease itself, predicting hemorrhagic complications after surgery in patients with mild disease is difficult. This hereditary deficiency is characterized by prolongation of activated partial thromboplastin time with normal prothrombin time, and the demonstration of selective plasma factor XI deficit. Currently available products in the therapeutic arsenal are transfusion of fresh-frozen plasma, virus-inactivated factor XI concentrates, desmopressin (DDAVP) and antifibrinolytic drugs, whether alone or in combination. We describe a family with two affected children, in which the deficiency was identified as an autosomal recessive trait. Of the two patients, one required prophylactic treatment with desmopressin and tranexamic acid before surgery; the treatment was successful and no related complications were observed. The long-term outcome of individuals with this disease seems to be good with continuous follow up and early control of hemorrhagic episodes. Prophylactic therapy is not required, except when surgery is anticipated.
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PMID:[Familial study of factor XI deficiency. Presurgical prophylactic treatment with desmopressin plus antifibrinolytics]. 1239 75

To evaluate the hemostatic effects of desmopressin (DDAVP) in dogs with aspirin-induced platelet dysfunction and hemostatic impairment in chronic liver diseases, 3 microg/kg DDAVP was administrated subcutaneously. In aspirin-induced platelet dysfunction dogs (n=5), prolonged BMBT (buccal mucosal bleeding time) was shortened significantly after DDAVP injection (2.2 +/- 1.2 min, P<0.05). In dogs with chronic liver diseases (n=4), activated partial thromboplastin time (APTT) tended to shorten by 0.9 to 3.0 sec, and prolonged BMBT was shortened in two cases for 4.2 and 1.7 min after DDAVP injection. Therefore, the present results indicated that DDAVP shortened the prolonged BMBT in dogs with aspirin-induced platelet dysfunction and chronic liver disease. DDAVP might be helpful in hemostasis under invasive procedures such as biopsy or surgery for dogs with hemostatic impairment.
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PMID:Effects of DDAVP administrated subcutaneously in dogs with aspirin-induced platelet dysfunction and hemostatic impairment due to chronic liver diseases. 1257 9

Recessive type 3 von Willebrand disease (vWD) is a severe hemophilia-like bleeding disorder caused by homozygosity or double heterozygosity for two nonsense mutations (null alleles) and characterized by a strongly prolonged bleeding time (BT), absence of ristocetin-induced platelet aggregation (RIPA), absence of von Willebrand factor (vWF) protein, and prolonged activated partial thromboplastin time (APTT) due to factor VIII (FVIIIC): deficiency. Recessive severe type 1 vWD is caused by homozygosity or double heterozygosity for a missense mutation and differs from type 3 vWD by the detectable presence vWF:antigen (Ag) and FVIII:C levels between 0.09 and 0.40 U/mL. Carriers of one null allele or missense mutations are usually asymptomatic at vWF levels of 50% of normal. Mild recessive type 1 vWD may be due to a missense mutations, or one missense mutation plus blood group O. The so-called dominant type 1 vWD secretion defect and type 1 Vicenza are caused by a heterozygous missense mutation in the vWF gene that produces a mutant vWF protein having a dominant effect on the normal vWF protein produced by the normal vWF allele with regard to the defective processing, storage secretion, and/or proteolysis of vWF in endothelial cells and clearing from plasma consistent with a type 2 phenotype of vWD. Typical type 2 vWD patients, except 2N, show a defective vWF protein, decreased ratios for vWF:ristocetin cofactor [vWF:RCo]/vWF:Ag and vWF:collagen binding factor [vWF:CB]/vWF:Ag and prolonged BT. The BT is normal and FVIII:C levels clearly are lower than vWF:Ag in type 2N vWD. Multimeric analysis of vWF in plasma demonstrates that proteolysis of vWF is increased in type 2A and 2B vWD, with increased triplet structure of each band (not present in types 2M and 2U). Proteolysis of vWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. vWD 2B differs from 2A by normal vWF in platelets, and increased RIPA. RIPA is normal in mild, decreased in moderate, and absent in severe type 2A vWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D; variable in 2E; and normal in 2N and dominant type 1. vWD 2M is usually mild and features decreased vWF:RCo and RIPA, and a normal or near-normal vWF multimeric pattern in a low-resolution agarose gel. vWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically features low vWF:RCo and RIPA with the relative lack of large vWF multimers. vWD type 2C is recessive; the dominant type 2D is rare. The response to desmopressin acetate (DDAVP) of vWF parameters is normal in pseudo-vWD and mild type 1. The responses to DDAVP of FVIII:C and vWF parameters in vWD 2M, Vincenza, 2E, and mild 2A, 2U, and 2N are transiently good for a variable number of hours to arrest mucocutaneous bleeding episodes or to prevent bleeding during minor surgery or trauma. However, the responses are not good enough to treat major bleedings or to prevent bleeding during major surgery or trauma. The response to DDAVP of vWF parameters is poor in recessive type 3, 1 and 2C, and dominant 2A, 2B, and 2U. Proper recommendations of FVIII/vWF concentrates using FVIII:C and vWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes in type 2 disease that is nonresponsive to DDAVP and in type 3 vWD are proposed.
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PMID:Characterization, classification, and treatment of von Willebrand diseases: a critical appraisal of the literature and personal experiences. 1627 67


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